%0 Journal Article
%T A Subanesthetic Dose of Isoflurane during Postconditioning Ameliorates Zymosan-Induced Neutrophil Inflammation Lung Injury and Mortality in Mice
%A Hui Wang
%A Jing Fan
%A Nan-lin Li
%A Jun-tang Li
%A Shi-fang Yuan
%A Jun Yi
%A Ling Wang
%A Jiang-hao Chen
%A Yong-gang Lv
%A Qing Yao
%A Ting Wang
%A Yu-cai Wang
%A Rui Ling
%J Mediators of Inflammation
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/479628
%X Anesthetic isoflurane (ISO) has immunomodulatory effects. In the present study, we investigated whether a subanesthetic dose of ISO (0.7%) protected against zymosan (ZY) induced inflammatory responses in the murine lung and isolated neutrophils. At 1 and 6ˋhrs after ZY administration intraperitoneally, ISO was inhaled for 1ˋhr, and 24ˋhrs later, lung inflammation and injury were assessed. We found that ISO improved the survival rate of mice and mitigated lung injury as characterized by the histopathology, wet-to-dry weight ratio, protein leakage, and lung function index. ISO significantly attenuated ZY-induced lung neutrophil recruitment and inflammation. This was suggested by the downregulation of (a) endothelial adhesion molecule expression and myeloperoxidase (MPO) activity in lung tissue and polymorphonuclear neutrophils (b) chemokines, and (c) proinflammatory cytokines in BALF. Furthermore, ZY-induced nuclear translocation and DNA-binding activity of NF-百B p65 were also reduced by ISO. ISO treatment inhibited iNOS expression and activity, as well as subsequent nitric oxide generation. Consistent with these in vivo observations, in vitro studies confirmed that ISO blocked NF-百B and iNOS activation in primary mouse neutrophils challenged by ZY. These results provide evidence that 0.7% ISO ameliorates inflammatory responses in ZY-treated mouse lung and primary neutrophils. 1. Introduction Multiple organ dysfunction syndrome (MODS) leads to high morbidity and mortality rates in the intensive care unit and is one of the most urgent and challenging public health problems worldwide [1, 2]. The lung is frequently the first organ that fails during the development of this syndrome. However, the mechanism of lung injury induced by inflammation remains to be determined, and the therapeutic regimen requires further investigation. Zymosan-induced generalized inflammation (ZIGI) mouse model can reproduce many characteristics of human MODS, which is adopted by many research groups [3, 4]. Several reports have shown that the onset of ZY-induced inflammatory response in mouse lung is associated with the gas exchange barrier and that it culminates with maximal neutrophil accumulation, exudate formation, and proinflammatory cytokines production [5每7]. ZY is recognized by toll-like receptor 2 (TLR-2) on immune cells (e.g., neutrophils), which subsequently trigger signal cascade for nuclear factor-百B (NF-百B) activation [8]. NF-百B activation is required for maximal expression of many proinflammatory cytokines and chemokines and iNOS involved in the pathogenesis of acute
%U http://www.hindawi.com/journals/mi/2013/479628/